Tumor bearing hosts exhibit variable immune responses to their autologous tumors. In some cases these responses are effective in rejecting the tumor; however, in most cases, the immune response is weak and ineffective. The goal of the proposed studies is to enhance tumor-specific immune responses such that tumors are rejected by the autologous host. Recent studies from this lab demonstrate that a malignant mouse sarcoma can be rejected by the autologous (strain of origin) host following transfection and expression in tumor cells of syngeneic major histocompatibility complex (MHC) class II genes. The class II transfectants protect susceptible mice against future and simultaneous wild type tumor challenges, and can rescue mice carrying the wild type tumor. Induction of class II antigen expression in tumor cells therefore significantly enhances tumor immunogenicity in this sarcoma system, and provides a potential strategy for tumor-specific immunotherapy. In order to exploit class II transfection as a method of immunotherapy, we will establish a mouse model system in which to further test the effectiveness of class II antigen induction in enhancing tumor-specific immunity. This goal will be accomplished by 1) further testing the role of I-A and I-E MHC class II antigen expression in autologous tumor immunity to solid tumors and non- sarcoma tumors; 2) determining the mechanisms by which the class II+ transfectants enhance tumor-specific immunity; and 3) determining the in vivo conditions under which class II antigen induction can be exploited for specific immunotherapy. These studies will establish a mouse model system for testing the potential usefulness of this promising and novel strategy for tumor specific immunotherapy.